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. 2010 Jun 7:10:154.
doi: 10.1186/1471-2334-10-154.

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

Marlo Möller  1 , Almut Nebel, Paul D van Helden, Stefan Schreiber, Eileen G Hoal
Affiliations

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

Marlo Möller et al. BMC Infect Dis. .

Abstract

Background: Interferon gamma is a major macrophage-activating cytokine during infection with Mycobacterium tuberculosis, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as M. tuberculosis. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.

Methods: Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System, capillary electrophoresis of fluorescently labelled PCR products, TaqMan SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.

Results: A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.

Conclusions: This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.

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Figures

Figure 1
Figure 1
Plot of LD between IL12B markers analysed in control individuals of the SAC population. Generated by Haploview v4.1. The 5' and 3' ends of the genes are indicated and r2 values (%) are shown on the squares (no value = 100%). The colours of the squares represent D' values, with dark grey being D' = 1, and white D' = 0.
See this image and copyright information in PMC

References

    1. Comstock GW. Tuberculosis in twins: a re-analysis of the Prophit survey. Am Rev Respir Dis. 1978;117:621–624. - PubMed
    1. Jepson A, Fowler A, Banya W, Singh M, Bennett S, Whittle H, Hill AV. Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis a study of twins in West Africa. Infect Immun. 2001;69:3989–3994. doi: 10.1128/IAI.69.6.3989-3994.2001. - DOI - PMC - PubMed
    1. Kallmann FJ, Reisner D. Twin studies on the significance of genetic factors in tuberculosis. Am Rev Tuberc. 1942;47:549–547.
    1. Newport MJ, Goetghebuer T, Weiss HA, Whittle H, Siegrist CA, Marchant A. Genetic regulation of immune responses to vaccines in early life. Genes Immun. 2004;5:122–129. doi: 10.1038/sj.gene.6364051. - DOI - PubMed
    1. Kimman TG, Janssen R, Hoebee B. Future prospects in respiratory syncytial virus genetics. Future Virology. 2006;1:483–492. doi: 10.2217/17460794.1.4.483. - DOI

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